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5-HT2 Receptors and 5-HIAA—Therapeutic Targets for Evaluation of Severity, Progression and Effectiveness of Treatment In Immature Male Rats in a Monocrotalin Model of Pulmonary Hypertension

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Abstract

Suppression of the proliferation of vascular endothelial cells and the interaction of endothelial with smooth muscle cells in pulmonary hypertension (PH) are impaired. Participation of the 5-HT2a receptor in the mitogenic effect on endothelial, and 5-HT2b receptor—on vascular smooth muscle cells was revealed. The main organ that metabolizes serotonin is the lung. In the endothelial cells of the vessels of the lungs under the action of the enzyme monoamine oxidase And serotonin is converted to 5-hydroxyindoleacetic acid (5-HIAA), which is subsequently excreted in the urine. Currently, the role of 5 -HT 2 receptors is not taken into account in the treatment of children with pulmonary hypertension. We have modified the monocrotaline model of pulmonary hypertension for immature rats. A scheme for the administration of a 5-HT2 receptor blocker for the prevention and treatment of pulmonary hypertension in immature rats was developed and tested. A positive correlation was found between the concentration of 5-HIAA in urine and the degree of pulmonary hypertension, which can become a potential marker of pulmonary hypertension. The data obtained indicate the development of pulmonary hypertension in immature rats after a single injection of monocrotaline in the form of replacement of lung tissue with fibrous tissue, the development of pneumosclerosis and bronchiectasis. Also, in animals in this model, changes in the structure of the heart muscle and vascular wall are formed with the development of fibrous tissue, which may indicate the involvement of 5HT2 -receptors in the activation of fibroblasts and, accordingly, in the pathogenesis of pulmonary hypertension.

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Funding

The study was supported by the Russian Science Foundation grant No. 23-15-00417, https://rscf.ru/project/23-15-00417/.

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Authors and Affiliations

  1. Kazan State Medical University, Kazan, Republic of Tatarstan, Russia

    D. F. Bilalova, R. R. Nigmatullina & A. A. Mustafin

  2. Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, Kazan, Republic of Tatarstan, Russia

    A. A. Mustafin

Authors
  1. D. F. Bilalova
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  2. R. R. Nigmatullina
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  3. A. A. Mustafin
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Contributions

Development of the concept of work and planning of the experiment (Mustafin A.A., Nigmatullina R.R., Bilalova D.F.), data collection (Bilalova D.F., Mustafin A.A., Nigmatul-lina R.R.,), processing data (Bilalova D.F., Mustafin A.A., Nigmatullina R.R.), writing and editing the article (Mustafin A.A., Nigmatullina R.R., Bilalova D.F.).

The authors agree to be responsible for all aspects of the work, and also guarantee that all questions about the validity and reliability of any part of the work are properly analyzed and resolved.

Corresponding author

Correspondence to D. F. Bilalova.

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COMPLIANCE WITH ETHICAL STANDARDS

All applicable international, national and/or institutional guidelines for the care and use of animals have been followed. All procedures performed in studies involving animals met the ethical standards approved by the legal acts of the Russian Federation, the principles of the Basel Declaration and the recommendations of the local ethics committee of the Kazan State Medical University protocol No. 3 dated 03/22/2022.

This article does not contain any research involving humans as research subjects.

CONFLICT OF INTEREST

The authors declare no financial or other conflicts of interest.

Diana Faridovna Bilalova wrote the first version of the manuscript. The fee for the release of the manuscript was not paid to anyone.

Additional information

Translated by A. Polyanovsky

Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 8, pp. 1045–1055https://doi.org/10.31857/S0869813923080022.

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Bilalova, D.F., Nigmatullina, R.R. & Mustafin, A.A. 5-HT2 Receptors and 5-HIAA—Therapeutic Targets for Evaluation of Severity, Progression and Effectiveness of Treatment In Immature Male Rats in a Monocrotalin Model of Pulmonary Hypertension. J Evol Biochem Phys 59, 1374–1381 (2023). https://doi.org/10.1134/S0022093023040282

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